Children and pregnant women bear the greatest burden of malaria in sub-Saharan Africa. Pregnancy is a unique period of malaria vulnerability during adulthood. Malaria in pregnancy is associated with increased rates of maternal anemia, low birth weight in the infant and increased infant mortality. One long-used method to prevent malaria in pregnancy is the administration of antimalarial medication during pregnancy either to prevent malaria or to intermittently treat malaria infection in women without evidence of disease. Chloroquine has been used in weekly chemoprophylaxis to prevent pregnancy-associated malaria. With the global spread of resistance, chloroquine lost its efficacy both for preventing infection and treating disease and the antifolate combination sulfadoxine-pyrimethamine (SP) took its place. Rather than aiming to prevent infection with medication, a strategy of intermittent preventive therapy in pregnancy (IPTp) was implemented using SP. In IPTp, a curative dose of SP is administered at regular intervals during pregnancy to cure any malaria infection that is present, regardless of clinical symptoms. Due to the spread of chloroquine resistance and the toxicity of weekly SP, the alternative strategies of continuous suppressive chemoprophylaxis and IPTp have not been directly compared using the same drug. We have a unique opportunity to compare these strategies in Malawi, where we recently discovered that twelve years after chloroquine was withdrawn due to high rates of resistance, chloroquine-resistant parasites predominate and chloroquine is once again an effective agent to treat malaria in Malawi. The overall goal of this study is to establish the optimal strategy for administering antimalarial medication to prevent pregnancy-associated malaria and avoid its detrimental effects on mothers and newborn children. [unreadable] [unreadable] This application for a Clinical Trial Planning Grant is submitted to prepare for a randomized, controlled clinical trial of weekly chloroquine chemoprophylaxis vs. chloroquine IPTp vs. SP IPTp. The specific aims for the one-year planning period are: (1) to develop a clinical protocol, data safety and monitoring plan and informed consent document that is approved by the Division of Microbiology and Infectious Diseases (DMID) and the affiliated Institutional Review Boards and Ethics Committees (IRB/EC), (2) to produce a manual of procedures for all study-related activities (3) to generate a data management system, (4) to generate training material and schedule for the study staff and (5) to create a budget for the clinical trial. [unreadable] [unreadable] [unreadable]